We have investigated the mechanism by which flavone-8-acetic acid (FAA) acts to enhance immune responsiveness in murine tumor model systems. Analysis of spleen mRNA samples after FAA administration indicates that both interferon (IFN) alpha and tumor necrosis factor (TNF) mRNA can be detected within 1-3 hours. Further studies have indicated that flavone can act directly on mouse spleen cells in vitro. These results indicate that FAA is a potent biological response modifier which acts by directly stimulating gene expression of important immunoregulatory proteins.